Serum irisin concentration in women with gestational diabetes.

Irisin is a novel myokine and adipokine which induces an increase in total body energy expenditure, improving insulin sensitivity and glucose tolerance in experimental animals. In the present study, serum irisin concentration was measured by an enzyme immunoassay in 130 women with gestational diabetes mellitus (GDM) and 140 BMI-matched patients with normal glucose tolerance (NGT). Median irisin level was significantly lower in the patients with GDM than in the NGT subjects (1703.3 [1354.8-2097.9 ng/ml] versus 1873.8 [1519.8-2294.8 ng/ml], p = 0.01); however, 3 months after childbirth its concentrations did not differ markedly between the two groups (1165.9 [872.1-1497.5] ng/ml versus 1139.0 [984.0-1376.7] ng/ml). In the whole group, irisin concentration correlated negatively with 2 h glucose level (R = -0.14, p = 0.03). In the women with NGT, irisin concentration correlated positively with IS(OGTT) (R = 0.22, p = 0.04) and the disposition index (DI(120)) (R = 0.24, p = 0.03), as well as negatively with 2 h insulin level (R = -0.23, p = 0.03) and HOMA-IR (R = -0.24, p = 0.02). Multiple regression analysis revealed that 2 h glucose and DI(120) were the only variables significantly influencing serum irisin (ß = 0.158, p = 0.03 and ß = 0.159, p = 0.02, respectively). Our results suggest that serum irisin concentration increases markedly in pregnant women, but this increase seems to be significantly lower in patients with GDM.

The expression of suppressor of cytokine signaling 1 and 3 in fat and placental tissue from women with gestational diabetes.

The suppressor of cytokine signaling (SOCS) proteins are feedback inhibitors of signaling pathways induced by cytokines, hormones and growth factors. In the present study we measured the expression of SOCS1, SOCS3, interleukin-6 (IL-6), IL-6 receptor, IL-8 and leptin mRNA in paired samples of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue obtained from 18 pregnant women with normal glucose tolerance (NGT) and 20 subjects with gestational diabetes mellitus (GDM), using quantitative RT-PCR. The patients with GDM had significantly higher IL-8 mRNA expression in VAT than the women with NGT (p = 0.007), whereas the expression of SOCS1, SOCS3 and other genes study did not differ significantly between the two groups. Stepwise regression analysis revealed that SOCS1 mRNA expression in VAT was significantly associated with prepregnancy BMI (ß = -0.68, p = 0.03) and IL-8 mRNA expression (ß = 0.66, p = 0.03), whereas SOCS3 mRNA expression in VAT was independently predicted by IL-6 mRNA expression (ß = 0.94, p = 0.0002, R(2) = 0.88). In conclusion, our results did not show significant differences in SOCS1 and SOCS3 mRNA expression in adipose and placental tissue obtained from pregnant women with and without GDM.

The association of bone turnover markers with pro- and anti-inflammatory adipokines in patients with gestational diabetes.

OBJECTIVE: The aim of the study was to assess differences in circulating osteocalcin (OC) and osteoprotegerin (OPG), as well as in their expression in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue obtained from patients with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT). MATERIALS AND METHOD: Serum levels of OC, OPG and soluble nuclear factor-kB ligand (sRANKL) were measured in 49 women with GDM and 30 subjects with NGT between weeks 24-32 of gestation, and three months after childbirth. OC and OPG mRNA expression was measured in 23 patients with GDM and 23 women with NGT at term, using quantitative real-time RT-PCR. RESULTS: The patients with GDM had decreased OC mRNA expression in SAT (p=0.015), lower adiponectin mRNA expression in VAT (p=0.039), and a lower circulating adiponectin level (p=0.04). Multiple regression analysis revealed that serum adiponectin was significantly associated with OC mRNA expression in SAT (b=0.49, p=0.03). Three months postpartum, the OPG/sRANKL ratio was markedly higher in the subjects with prior GDM (p=0.03) and correlated positively with HbA1c (R=0.33; p=0.04), fasting insulin (R=0.35; p=0.03) and HOMA-IR (R=0.34; p=0.04). CONCLUSIONS: In the patients with GDM decreased OC mRNA expression in SAT might be associated with a reduced stimulatory effect on adiponectin expression in adipose tissue. On the other hand, higher OPG/sRANKL ratio suggests a better protection against bone loss in the subjects with prior GDM.

Increased Maternal and Cord Blood Betatrophin in Gestational Diabetes.

AIM: The aim of the study was to compare maternal and cord blood levels of betatrophin--a new peptide potentially controlling beta cell growth--as well as in its mRNA expression in subcutaneous adipose tissue, visceral adipose tissue and placental tissue obtained from pregnant women with normal glucose tolerance (NGT) and gestational diabetes (GDM). METHODS: Serum betatrophin and irisin concentrations were measured by ELISA in 93 patients with GDM and 97 women with NGT between 24 and 28 week of gestation. Additionally, maternal and cord blood betatrophin and irisin, as well as their genes (C19orf80 and Fndc5) expression were evaluated in 20 patients with GDM and 20 women with NGT at term. RESULTS: In both groups, serum betatrophin concentrations were significantly higher in the patients with GDM than in the controls (1.91 [1.40-2.60] ng/ml vs 1.63 [1.21-2.22] ng/ml, p=0.03 and 3.45 [2.77-6.53] ng/ml vs 2.78 [2.16-3.65] ng/ml, p=0.03, respectively). Cord blood betatrophin levels were also higher in the GDM than in the NGT group (20.43 [12.97-28.80] ng/ml vs 15.06 [10.11-21.36] ng/ml, p=0.03). In both groups betatrophin concentrations in arterial cord blood were significantly higher than in maternal serum (p=0.0001). Serum irisin levels were significantly lower in the patients with GDM (1679 [1308-2171] ng/ml) than in the healthy women between 24 and 28 week of pregnancy (1880 [1519-2312] ng/ml, p=0.03). Both C19orf80 and Fndc5 mRNA expression in fat and placental tissue did not differ significantly between the groups studied. CONCLUSIONS: Our results suggest that an increase in maternal and cord blood betatrophin might be a compensatory mechanism for enhanced insulin demand in GDM.

The IL-6/IL-6R/sgp130 system and Th17 associated cytokines in patients with gestational diabetes.

INTRODUCTION: Interleukin-6 (IL-6) is a pleiotropic cytokine which signals through a cell surface receptor complex consisting of a cognatereceptor subunit (IL-6R) and glycoprotein 130 (gp130), which is considered an antagonist to the IL-6R/IL-6 pathway. The aim of the present study was to assess IL-6/IL-6R/gp130 system and Th17 associated cytokines in different time points during and after pregnancy in women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT). MATERIAL AND METHODS: Serum levels of IL-6, sIL6R, sgp130, IL-17 and IL-23 were measured in 91 women divided into three groups: GDMin the 24th-28th week of gestation (visit 1), NGT at the 1st visit and GDM in the 29th-32nd week, and NGT at both visits. RESULTS: The patients with GDM recognised at the 1st visit had significantly higher IL-6 (p = 0.02) and sgp130 (p = 0.03) concentrations than had the women with NGT, whereas the women with GDM diagnosed at the 2nd visit had elevated sIL-6R concentrations (p = 0.03). The patients with low sIL-6R but high sgp130 concentration had significantly higher glucose levels (p = 0.04) and lower IL-6 values (p = 0.04) than had the patients with low sIL-6R and sgp130 concentrations. IL-17 and IL-23 were detected in approximately one-third of the population studied. A trend towards higher IL-17 levels was observed in the subjects with GDM, but the differences were not significant. CONCLUSIONS: Our results suggest that an increased serum sgp130 concentration in the patients with GDM might represent a compensatory mechanism, controlling intracellular IL-6 signalling and preventing the activation of the IL-6/IL-6R pathway.

The expression of genes involved in NF-κB activation in peripheral blood mononuclear cells of patients with gestational diabetes.

OBJECTIVE: In patients with obesity and type 2 diabetes, the changes in insulin resistance are associated with the changes in expression of genes involved in nuclear factor-κB (NF-κB) activation in peripheral blood mononuclear cells (PBMCs). As such studies have never been carried out in patients with gestational diabetes (GDM), in this study, we evaluated the expression of genes involved in NF-κB activation and related to glucose metabolism in PBMCs obtained from pregnant women with GDM and normal glucose tolerance (NGT). DESIGN AND METHODS: RT-PCR was performed in 60 pregnant women divided into three groups: GDM at the 1st visit, i.e. in the 24th-28th weeks of gestation (GDM1), NGT at the first visit and GDM in the 29th-32nd weeks (GDM2), and NGT at both visits. The tests were repeated 3 months postpartum. RESULTS: The GDM1 group had significantly higher TLR2 (P=0.024), TLR4 (P=0.037), STAT1 (P=0.027), and CX3CL1 (P=0.017) mRNA expression, whereas the GDM2 group showed markedly lower TNFRSF1A (P=0.042), PPARG (P=0.018), STAT3 (P=0.013), and CX3CL1 (P=0.038) mRNA expression in comparison with the NGT group. The women with NGT at the 1st visit who later developed GDM had significantly higher fasting glucose (P=0.01), HOMA-IR (P=0.004), and TLR2 mRNA expression (P=0.04), as well as lower ISSI2 (P=0.01) and disposition indices, DI30 (P=0.03) and DI120 (P=0.01), than had the women who remained normoglycemic. CONCLUSIONS: Our results suggest that elevated TLR2 expression, as well as higher fasting glucose and lower compensation for increased insulin resistance, may represent early metabolic disturbances in the development of GDM.